AVAHO

Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

Sex-specific treatment strategies may prolong survival and improve outcomes in male and female patients with glioblastoma, investigators suggest after a retrospective analysis.

In an analysis of data from 63 men and women with glioblastoma, the researchers found that a significant reduction in tumor growth velocity during standard chemotherapeutic treatment was seen only for females patients with glioblastoma (P = .02569). In addition, they reported that for female patients, a reduction in tumor growth velocity was linked with significantly increased survival versus higher velocity growth (median survival, 3090 days vs. 681 days; P = .00817).

In contrast, the men in the study showed no statistically significant correlation between survival and velocity, the investigators reported.

The researchers analyzed data from 63 patients with glioblastoma using clinical information from a research database at the Mayo Clinic in Phoenix. They also incorporated transcriptome data, which was connected via an electronic algorithm, and were able to detect certain molecular variations of glioblastoma that are integral components of survival for individuals with the disease. From these findings, Wei Yang, PhD, of Washington University, St. Louis, along with his colleagues, were able to validate links between the effects of chemotherapy and gene expression.

“We measured sex differences in the in vitro cytotoxic effects of four common chemotherapeutics in a panel of nine (five male and four female) patient-derived glioblastoma cell isolates,” the investigators said in Science Translational Medicine.

The authors acknowledged a key limitation of the study was the retrospective nature of the imaging analysis, which has the potential to introduce interoperator differences in tumor growth velocity measurements. With these limitations, Dr. Yang and his colleagues highlighted the importance of ensuring imaging data is verified by trained professionals.

“Together, these results suggest that greater precision in glioblastoma molecular subtyping can be achieved through sex-specific analyses and that improved outcomes for all patients might be accomplished by tailoring treatment to sex differences in molecular mechanisms,” they concluded.

The study was supported by grant funding from the National Institutes of Health, Children’s Discovery Institute of Washington University, James S. McDonnell Foundation, Ivy Foundation, Ben & Catherine Ivy Foundation, and the Mayo Clinic. Albert H. Kim and Kristin R. Swanson reported financial affiliations with Monterris and the James S. McDonnell Foundation. Other authors reported no conflicts of interest related to the work.

SOURCE: Yang W et al. Sci Transl Med. 2019 Jan 02. doi: 10.1126/scitranslmed.aao5253.

Sex-specific treatment strategies may prolong survival and improve outcomes in male and female patients with glioblastoma, investigators suggest after a retrospective analysis.

In an analysis of data from 63 men and women with glioblastoma, the researchers found that a significant reduction in tumor growth velocity during standard chemotherapeutic treatment was seen only for females patients with glioblastoma (P = .02569). In addition, they reported that for female patients, a reduction in tumor growth velocity was linked with significantly increased survival versus higher velocity growth (median survival, 3090 days vs. 681 days; P = .00817).

In contrast, the men in the study showed no statistically significant correlation between survival and velocity, the investigators reported.

The researchers analyzed data from 63 patients with glioblastoma using clinical information from a research database at the Mayo Clinic in Phoenix. They also incorporated transcriptome data, which was connected via an electronic algorithm, and were able to detect certain molecular variations of glioblastoma that are integral components of survival for individuals with the disease. From these findings, Wei Yang, PhD, of Washington University, St. Louis, along with his colleagues, were able to validate links between the effects of chemotherapy and gene expression.

“We measured sex differences in the in vitro cytotoxic effects of four common chemotherapeutics in a panel of nine (five male and four female) patient-derived glioblastoma cell isolates,” the investigators said in Science Translational Medicine.

The authors acknowledged a key limitation of the study was the retrospective nature of the imaging analysis, which has the potential to introduce interoperator differences in tumor growth velocity measurements. With these limitations, Dr. Yang and his colleagues highlighted the importance of ensuring imaging data is verified by trained professionals.

“Together, these results suggest that greater precision in glioblastoma molecular subtyping can be achieved through sex-specific analyses and that improved outcomes for all patients might be accomplished by tailoring treatment to sex differences in molecular mechanisms,” they concluded.

The study was supported by grant funding from the National Institutes of Health, Children’s Discovery Institute of Washington University, James S. McDonnell Foundation, Ivy Foundation, Ben & Catherine Ivy Foundation, and the Mayo Clinic. Albert H. Kim and Kristin R. Swanson reported financial affiliations with Monterris and the James S. McDonnell Foundation. Other authors reported no conflicts of interest related to the work.

SOURCE: Yang W et al. Sci Transl Med. 2019 Jan 02. doi: 10.1126/scitranslmed.aao5253.

Sex-specific treatment strategies may prolong survival and improve outcomes in male and female patients with glioblastoma, investigators suggest after a retrospective analysis.

In an analysis of data from 63 men and women with glioblastoma, the researchers found that a significant reduction in tumor growth velocity during standard chemotherapeutic treatment was seen only for females patients with glioblastoma (P = .02569). In addition, they reported that for female patients, a reduction in tumor growth velocity was linked with significantly increased survival versus higher velocity growth (median survival, 3090 days vs. 681 days; P = .00817).

In contrast, the men in the study showed no statistically significant correlation between survival and velocity, the investigators reported.

The researchers analyzed data from 63 patients with glioblastoma using clinical information from a research database at the Mayo Clinic in Phoenix. They also incorporated transcriptome data, which was connected via an electronic algorithm, and were able to detect certain molecular variations of glioblastoma that are integral components of survival for individuals with the disease. From these findings, Wei Yang, PhD, of Washington University, St. Louis, along with his colleagues, were able to validate links between the effects of chemotherapy and gene expression.

“We measured sex differences in the in vitro cytotoxic effects of four common chemotherapeutics in a panel of nine (five male and four female) patient-derived glioblastoma cell isolates,” the investigators said in Science Translational Medicine.

The authors acknowledged a key limitation of the study was the retrospective nature of the imaging analysis, which has the potential to introduce interoperator differences in tumor growth velocity measurements. With these limitations, Dr. Yang and his colleagues highlighted the importance of ensuring imaging data is verified by trained professionals.

“Together, these results suggest that greater precision in glioblastoma molecular subtyping can be achieved through sex-specific analyses and that improved outcomes for all patients might be accomplished by tailoring treatment to sex differences in molecular mechanisms,” they concluded.

The study was supported by grant funding from the National Institutes of Health, Children’s Discovery Institute of Washington University, James S. McDonnell Foundation, Ivy Foundation, Ben & Catherine Ivy Foundation, and the Mayo Clinic. Albert H. Kim and Kristin R. Swanson reported financial affiliations with Monterris and the James S. McDonnell Foundation. Other authors reported no conflicts of interest related to the work.

SOURCE: Yang W et al. Sci Transl Med. 2019 Jan 02. doi: 10.1126/scitranslmed.aao5253.

SAN DIEGO – The majority of pediatric patients with mixed phenotype acute leukemia (MPAL) who were treated with acute lymphoblastic leukemia (ALL)–directed chemotherapy achieved a minimum residual disease (MRD)–negative complete response by the end of consolidation, according to findings from a multicenter retrospective cohort study.

Sharon Worcester/MDedge News

The cohort included 94 patients aged 1-21 years who met strict World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions. Most had B/myeloid phenotype (89%), and 87 patients were treated with an ALL regimen, Etan Orgel, MD, reported at the annual meeting of the American Society of Hematology.

Of those 87 patients, 81 (93%) experienced an end-of-induction (EOI) complete response. One patient died during induction and six had induction failures, defined as either disease progression before EOI (two patients) or EOI MRD of 5% or greater (three patients), said Dr. Orgel of the University of Southern California, Los Angeles, and Children’s Hospital Los Angeles.

The MRD-negative rates, defined as MRD less than 0.01%, were 70% at EOI and 86% at EOI or end of consolidation (EOC); 12 of 14 patients who were MRD positive at EOI and continued on ALL therapy achieved an EOC MRD-negative complete response, including 8 of 8 with EOI MRD of 0.01%-0.09% and 4 of 6 with EOI MRD of 1% or greater.

Event-free survival at 5 years in the 78 patients without hematopoietic stem cell transplant at first remission was 75%, and 5-year overall survival was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said. “This is very different from the approach used at many adult centers and many of the adult recommendations.”

Overall 5-year EOI event-free survival was 80% in the 59 patients who were MRD negative at EOI, and 13% in 25 patients who were MRD-positive at EOI. The corresponding overall survival rates were 91% and 84%.

Overall 5-year EOC event-free survival was 77% in 74 patients who were MRD negative at EOC and was unavailable in 3 patients who were MRD positive at EOC, although all three were salvaged. The corresponding EOC overall survival rates were 89% and “not available,” Dr. Orgel reported.

Multivariable analysis confirmed the predictive value of MRD at EOI (hazard ratio for event-free survival and overall survival, 3.77 and 3.54, respectively).

Of note, there was a possible trend toward earlier failure and a trend toward worse overall survival (HR, 4.49, P = .074) for T-lineage–containing MPAL.

“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” he said.

MRD in pediatric MPAL is rare. Recent studies of MPAL biology show areas of similarity with ALL and AML, and while this could eventually help further subcategorize or classify the disease and lead to biology-driven therapies, it is important to know how to treat the disease today, Dr. Orgel said.

The evolving consensus is that ALL therapy is adequate for most MPAL, but there is no established threshold for MRD to enable a risk-stratified MPAL approach, he added.

The current findings suggest that ALL therapy – without hematopoietic stem cell transplant – may be sufficient to treat most patients with pediatric MPAL, Dr. Orgen reported, noting that clinical trials are necessary to prospectively validate MRD thresholds at EOI and EOC and to establish the threshold for favorable survival.

“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” he said.

Dr. Orgel reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Oberley M et al. ASH 2018, Abstract 558.

SAN DIEGO – The majority of pediatric patients with mixed phenotype acute leukemia (MPAL) who were treated with acute lymphoblastic leukemia (ALL)–directed chemotherapy achieved a minimum residual disease (MRD)–negative complete response by the end of consolidation, according to findings from a multicenter retrospective cohort study.

Sharon Worcester/MDedge News

The cohort included 94 patients aged 1-21 years who met strict World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions. Most had B/myeloid phenotype (89%), and 87 patients were treated with an ALL regimen, Etan Orgel, MD, reported at the annual meeting of the American Society of Hematology.

Of those 87 patients, 81 (93%) experienced an end-of-induction (EOI) complete response. One patient died during induction and six had induction failures, defined as either disease progression before EOI (two patients) or EOI MRD of 5% or greater (three patients), said Dr. Orgel of the University of Southern California, Los Angeles, and Children’s Hospital Los Angeles.

The MRD-negative rates, defined as MRD less than 0.01%, were 70% at EOI and 86% at EOI or end of consolidation (EOC); 12 of 14 patients who were MRD positive at EOI and continued on ALL therapy achieved an EOC MRD-negative complete response, including 8 of 8 with EOI MRD of 0.01%-0.09% and 4 of 6 with EOI MRD of 1% or greater.

Event-free survival at 5 years in the 78 patients without hematopoietic stem cell transplant at first remission was 75%, and 5-year overall survival was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said. “This is very different from the approach used at many adult centers and many of the adult recommendations.”

Overall 5-year EOI event-free survival was 80% in the 59 patients who were MRD negative at EOI, and 13% in 25 patients who were MRD-positive at EOI. The corresponding overall survival rates were 91% and 84%.

Overall 5-year EOC event-free survival was 77% in 74 patients who were MRD negative at EOC and was unavailable in 3 patients who were MRD positive at EOC, although all three were salvaged. The corresponding EOC overall survival rates were 89% and “not available,” Dr. Orgel reported.

Multivariable analysis confirmed the predictive value of MRD at EOI (hazard ratio for event-free survival and overall survival, 3.77 and 3.54, respectively).

Of note, there was a possible trend toward earlier failure and a trend toward worse overall survival (HR, 4.49, P = .074) for T-lineage–containing MPAL.

“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” he said.

MRD in pediatric MPAL is rare. Recent studies of MPAL biology show areas of similarity with ALL and AML, and while this could eventually help further subcategorize or classify the disease and lead to biology-driven therapies, it is important to know how to treat the disease today, Dr. Orgel said.

The evolving consensus is that ALL therapy is adequate for most MPAL, but there is no established threshold for MRD to enable a risk-stratified MPAL approach, he added.

The current findings suggest that ALL therapy – without hematopoietic stem cell transplant – may be sufficient to treat most patients with pediatric MPAL, Dr. Orgen reported, noting that clinical trials are necessary to prospectively validate MRD thresholds at EOI and EOC and to establish the threshold for favorable survival.

“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” he said.

Dr. Orgel reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Oberley M et al. ASH 2018, Abstract 558.

SAN DIEGO – The majority of pediatric patients with mixed phenotype acute leukemia (MPAL) who were treated with acute lymphoblastic leukemia (ALL)–directed chemotherapy achieved a minimum residual disease (MRD)–negative complete response by the end of consolidation, according to findings from a multicenter retrospective cohort study.

Sharon Worcester/MDedge News

The cohort included 94 patients aged 1-21 years who met strict World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions. Most had B/myeloid phenotype (89%), and 87 patients were treated with an ALL regimen, Etan Orgel, MD, reported at the annual meeting of the American Society of Hematology.

Of those 87 patients, 81 (93%) experienced an end-of-induction (EOI) complete response. One patient died during induction and six had induction failures, defined as either disease progression before EOI (two patients) or EOI MRD of 5% or greater (three patients), said Dr. Orgel of the University of Southern California, Los Angeles, and Children’s Hospital Los Angeles.

The MRD-negative rates, defined as MRD less than 0.01%, were 70% at EOI and 86% at EOI or end of consolidation (EOC); 12 of 14 patients who were MRD positive at EOI and continued on ALL therapy achieved an EOC MRD-negative complete response, including 8 of 8 with EOI MRD of 0.01%-0.09% and 4 of 6 with EOI MRD of 1% or greater.

Event-free survival at 5 years in the 78 patients without hematopoietic stem cell transplant at first remission was 75%, and 5-year overall survival was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said. “This is very different from the approach used at many adult centers and many of the adult recommendations.”

Overall 5-year EOI event-free survival was 80% in the 59 patients who were MRD negative at EOI, and 13% in 25 patients who were MRD-positive at EOI. The corresponding overall survival rates were 91% and 84%.

Overall 5-year EOC event-free survival was 77% in 74 patients who were MRD negative at EOC and was unavailable in 3 patients who were MRD positive at EOC, although all three were salvaged. The corresponding EOC overall survival rates were 89% and “not available,” Dr. Orgel reported.

Multivariable analysis confirmed the predictive value of MRD at EOI (hazard ratio for event-free survival and overall survival, 3.77 and 3.54, respectively).

Of note, there was a possible trend toward earlier failure and a trend toward worse overall survival (HR, 4.49, P = .074) for T-lineage–containing MPAL.

“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” he said.

MRD in pediatric MPAL is rare. Recent studies of MPAL biology show areas of similarity with ALL and AML, and while this could eventually help further subcategorize or classify the disease and lead to biology-driven therapies, it is important to know how to treat the disease today, Dr. Orgel said.

The evolving consensus is that ALL therapy is adequate for most MPAL, but there is no established threshold for MRD to enable a risk-stratified MPAL approach, he added.

The current findings suggest that ALL therapy – without hematopoietic stem cell transplant – may be sufficient to treat most patients with pediatric MPAL, Dr. Orgen reported, noting that clinical trials are necessary to prospectively validate MRD thresholds at EOI and EOC and to establish the threshold for favorable survival.

“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” he said.

Dr. Orgel reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Oberley M et al. ASH 2018, Abstract 558.

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

sworcester@mdedge.com

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

sworcester@mdedge.com

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

sworcester@mdedge.com

A negative colonoscopy result is associated with a reduced risk of colorectal cancer for more than 12 years after the examination, compared with an unscreened population, new research has found.

In a retrospective cohort study published in JAMA Internal Medicine, researchers analyzed data from 1,251,318 individuals at average risk of colorectal cancer who were eligible to participate in screening over more than 9 million person-years of follow-up.

They found that screened individuals with a negative result had an adjusted 46%-95% lower risk of colorectal cancer and 29%-96% lower risk of colorectal cancer mortality than unscreened individuals across more than 12 years of follow-up.

At 10 years post colonoscopy, participants who had a negative colonoscopy result still had a significant 46% lower risk of colorectal cancer and 88% lower risk of colorectal cancer mortality. After more than 12 years, there was still a nonsignificant trend towards a lower risk of colorectal cancer incidence and mortality.

Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco, and his coauthors suggested that their findings have implications for the timing of rescreening after a negative colonoscopy result.

“The current guideline-recommended 10-year rescreening interval is not based on a predetermined risk threshold, and while we observed a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, an examination of absolute risk [incidence] could provide another justification for the timing for rescreening,” they wrote. “Additional research is needed to evaluate the costs and benefits of earlier versus later rescreening, optimal rescreening tests following a negative colonoscopy result [e.g., another colonoscopy versus annual fecal immunochemical testing], and whether the benefits of rescreening vary between subgroups.”

The study showed that the rate of repeat endoscopic procedures increased at year 10, largely because of screening colonoscopies which are recommended at 10-year intervals. However in a separate analysis, the authors excluded colonoscopies for a screening indication and still found a similar reduction in the risk of colorectal cancer, compared with the unscreened group.

The data also showed a 22%-87% lower risk of proximal colorectal cancer, a 50%-99% lower risk of distal cancer, a 31%-95% lower risk of early-stage colorectal cancer, and a 56%-96% reduced risk of advanced-stage colorectal cancer among those who had a negative result, compared with those who did not undergo screening.

The authors wrote that this pattern of greater risk reductions in the distal versus proximal cancer had been seen in previous studies and could be the result of incomplete examinations, inadequate bowel cleansing, challenges in identifying right colon polyps and sessile serrated adenomas, or differences in polyp biology in the proximal versus distal colon.

The incidence rates of colorectal cancer among those who had a negative result from colonoscopy ranged from 16.6 per 100,000 person-years at 1 year after screening to 133.2 per 100,000 person-years at the 10-year mark. In comparison, the incidence rates among the unscreened population increased from 62.9 per 100,000 person-years at year 1 to 224.8 after year 12.

Mortality rates from colorectal cancer at year 1 were 6.8 per 100,000 person-years in the negative results group and 10.5 in the unscreened cohort. At year 12, that figure was 92.2 per 100,000 person-years in the negative results cohort, while after year 12 in the unscreened cohort, colorectal cancer mortality rates increased to 192 per 100,000 person years.

While the study made use of a validated cancer registry to ensure they accurately captured cancers and mortality, the authors acknowledged that they weren’t able to adjust for residual confounding factors such as red-meat intake or smoking.

The study was supported by the National Cancer Institute, the American Gastroenterological Association, and the Sylvia Allison Kaplan Foundation. No conflicts of interest were reported.

SOURCE: Lee JK et al. JAMA Intern Med. 2018 Dec 17. doi: 10.1001/jamainternmed.2018.5565.

A negative colonoscopy result is associated with a reduced risk of colorectal cancer for more than 12 years after the examination, compared with an unscreened population, new research has found.

In a retrospective cohort study published in JAMA Internal Medicine, researchers analyzed data from 1,251,318 individuals at average risk of colorectal cancer who were eligible to participate in screening over more than 9 million person-years of follow-up.

They found that screened individuals with a negative result had an adjusted 46%-95% lower risk of colorectal cancer and 29%-96% lower risk of colorectal cancer mortality than unscreened individuals across more than 12 years of follow-up.

At 10 years post colonoscopy, participants who had a negative colonoscopy result still had a significant 46% lower risk of colorectal cancer and 88% lower risk of colorectal cancer mortality. After more than 12 years, there was still a nonsignificant trend towards a lower risk of colorectal cancer incidence and mortality.

Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco, and his coauthors suggested that their findings have implications for the timing of rescreening after a negative colonoscopy result.

“The current guideline-recommended 10-year rescreening interval is not based on a predetermined risk threshold, and while we observed a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, an examination of absolute risk [incidence] could provide another justification for the timing for rescreening,” they wrote. “Additional research is needed to evaluate the costs and benefits of earlier versus later rescreening, optimal rescreening tests following a negative colonoscopy result [e.g., another colonoscopy versus annual fecal immunochemical testing], and whether the benefits of rescreening vary between subgroups.”

The study showed that the rate of repeat endoscopic procedures increased at year 10, largely because of screening colonoscopies which are recommended at 10-year intervals. However in a separate analysis, the authors excluded colonoscopies for a screening indication and still found a similar reduction in the risk of colorectal cancer, compared with the unscreened group.

The data also showed a 22%-87% lower risk of proximal colorectal cancer, a 50%-99% lower risk of distal cancer, a 31%-95% lower risk of early-stage colorectal cancer, and a 56%-96% reduced risk of advanced-stage colorectal cancer among those who had a negative result, compared with those who did not undergo screening.

The authors wrote that this pattern of greater risk reductions in the distal versus proximal cancer had been seen in previous studies and could be the result of incomplete examinations, inadequate bowel cleansing, challenges in identifying right colon polyps and sessile serrated adenomas, or differences in polyp biology in the proximal versus distal colon.

The incidence rates of colorectal cancer among those who had a negative result from colonoscopy ranged from 16.6 per 100,000 person-years at 1 year after screening to 133.2 per 100,000 person-years at the 10-year mark. In comparison, the incidence rates among the unscreened population increased from 62.9 per 100,000 person-years at year 1 to 224.8 after year 12.

Mortality rates from colorectal cancer at year 1 were 6.8 per 100,000 person-years in the negative results group and 10.5 in the unscreened cohort. At year 12, that figure was 92.2 per 100,000 person-years in the negative results cohort, while after year 12 in the unscreened cohort, colorectal cancer mortality rates increased to 192 per 100,000 person years.

While the study made use of a validated cancer registry to ensure they accurately captured cancers and mortality, the authors acknowledged that they weren’t able to adjust for residual confounding factors such as red-meat intake or smoking.

The study was supported by the National Cancer Institute, the American Gastroenterological Association, and the Sylvia Allison Kaplan Foundation. No conflicts of interest were reported.

SOURCE: Lee JK et al. JAMA Intern Med. 2018 Dec 17. doi: 10.1001/jamainternmed.2018.5565.

A negative colonoscopy result is associated with a reduced risk of colorectal cancer for more than 12 years after the examination, compared with an unscreened population, new research has found.

In a retrospective cohort study published in JAMA Internal Medicine, researchers analyzed data from 1,251,318 individuals at average risk of colorectal cancer who were eligible to participate in screening over more than 9 million person-years of follow-up.

They found that screened individuals with a negative result had an adjusted 46%-95% lower risk of colorectal cancer and 29%-96% lower risk of colorectal cancer mortality than unscreened individuals across more than 12 years of follow-up.

At 10 years post colonoscopy, participants who had a negative colonoscopy result still had a significant 46% lower risk of colorectal cancer and 88% lower risk of colorectal cancer mortality. After more than 12 years, there was still a nonsignificant trend towards a lower risk of colorectal cancer incidence and mortality.

Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco, and his coauthors suggested that their findings have implications for the timing of rescreening after a negative colonoscopy result.

“The current guideline-recommended 10-year rescreening interval is not based on a predetermined risk threshold, and while we observed a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, an examination of absolute risk [incidence] could provide another justification for the timing for rescreening,” they wrote. “Additional research is needed to evaluate the costs and benefits of earlier versus later rescreening, optimal rescreening tests following a negative colonoscopy result [e.g., another colonoscopy versus annual fecal immunochemical testing], and whether the benefits of rescreening vary between subgroups.”

The study showed that the rate of repeat endoscopic procedures increased at year 10, largely because of screening colonoscopies which are recommended at 10-year intervals. However in a separate analysis, the authors excluded colonoscopies for a screening indication and still found a similar reduction in the risk of colorectal cancer, compared with the unscreened group.

The data also showed a 22%-87% lower risk of proximal colorectal cancer, a 50%-99% lower risk of distal cancer, a 31%-95% lower risk of early-stage colorectal cancer, and a 56%-96% reduced risk of advanced-stage colorectal cancer among those who had a negative result, compared with those who did not undergo screening.

The authors wrote that this pattern of greater risk reductions in the distal versus proximal cancer had been seen in previous studies and could be the result of incomplete examinations, inadequate bowel cleansing, challenges in identifying right colon polyps and sessile serrated adenomas, or differences in polyp biology in the proximal versus distal colon.

The incidence rates of colorectal cancer among those who had a negative result from colonoscopy ranged from 16.6 per 100,000 person-years at 1 year after screening to 133.2 per 100,000 person-years at the 10-year mark. In comparison, the incidence rates among the unscreened population increased from 62.9 per 100,000 person-years at year 1 to 224.8 after year 12.

Mortality rates from colorectal cancer at year 1 were 6.8 per 100,000 person-years in the negative results group and 10.5 in the unscreened cohort. At year 12, that figure was 92.2 per 100,000 person-years in the negative results cohort, while after year 12 in the unscreened cohort, colorectal cancer mortality rates increased to 192 per 100,000 person years.

While the study made use of a validated cancer registry to ensure they accurately captured cancers and mortality, the authors acknowledged that they weren’t able to adjust for residual confounding factors such as red-meat intake or smoking.

The study was supported by the National Cancer Institute, the American Gastroenterological Association, and the Sylvia Allison Kaplan Foundation. No conflicts of interest were reported.

SOURCE: Lee JK et al. JAMA Intern Med. 2018 Dec 17. doi: 10.1001/jamainternmed.2018.5565.

With hundreds of sessions and thousands of abstracts, it can be difficult to wade through all the new findings to find the most significant and relevant findings. Federal Practitioner consulted with Association of VA Hematology/Oncology members who attended the meeting, VA researchers, and other sources to provide these nuggets you might have missed on lymphomas, white blood cells, leukemias, and multiple myeloma:

Lymphomas

Veterans Treated with R-CHOP for Diffuse Large B Cell Lymphoma Compared to Neighboring Hospital: An Interesting Discovery for Treatment Outcomes

This retrospective analysis of diffuse large B cell lymphoma (DCBL) patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the VA Audie Murphy Hospital in San Antonio, Texas was compared with patients with DLBCL who received R-CHOP in a community setting. According to the researchers, the response to initial treatment was inferior in the veteran population when compared with a patient population with similar demographics and having similar time from diagnosis to treatment. Veteran patients also had worse outcomes when compared with uninsured patients.

Factors Associated with Overall Survival in Follicular Lymphoma Patients Who Are Eligible for Maintenance Therapy

This retrospective analysis study identified 2,290 patients with follicular lymphoma treated in the Veterans Health Administration between 2006–2014 and detailed their staging, demographics, and comorbidities. The researchers found that maintenance therapy with rituximab was associated with an improvement in overall survival.

Treatment Practices and Outcomes in Older Adults with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Treated in the Veterans Health Administration

Another retrospective analysis of DBCL using VHA data examined the effectiveness of second-line chemotherapy and chemoimmunotherapy in patients aged ≥ 65 years. The researchers found 230 patients from 2001 to 2015 that met the inclusion criteria. According to the researchers, the overall survival was < 1 year and about half of the patients "did not receive or were not candidates for regimens typically used with intent for high-dose therapy and autologous transplant."

White Blood Cells

Cost-Effective Use of White Blood Cell Growth Factors in the Veterans Administration

This study analyzed the use of granulocyte colony-stimulating (G-CSF) vs pegfilgrastim in the UD Department of Veterans Affairs (VA) health care system. The researchers looked at the relative frequency of use of filgrastim, Tbo-filgrastim, Filgrastim-sndz and pegfilgrastim at 23 VA sites and found that uptake of biosimilar G-CSF has been extremely rapid. All sites are using biosimilar GCSF for all new patients; 6 of 23 sites were comfortable shifting current patients on branded G-CSF to the biosimilar.However, switching to a Tbo-filgrastim brought a cost savings of 2.2% that was "small compared to other clinical changes."

Elevated White Blood Cell Levels and Thrombotic Events in Patients with Polycythemia Vera: A Real-World Analysis of Veterans Health Administration Data

This analysis described the association between white blood cell (EBC) levels and occurrence of thrombotic events among patients with polycythemia vera (PV) using Veterans Health Administration claims data collected between 2005 and 2012. The researchers found A significant, positive association between increased WBC counts and occurrence of thrombotic events in patients with PV was observed in this study. Patients with WBC counts ≥ 8.5 × 109/L had a significantly increased risk of thrombotic events, and those with counts ≥ 11.0 × 109/L were at greatest risk. Effective control of WBC counts is an important component of disease management and may reduce risk of thrombotic events in patients with PV.

Leukemias

Survival and Treatment of Black Patients with Chronic Lymphocytic Leukemia in the Veterans Health Affairs

Black patients with chronic lymphocytic leukemia tend to have worse overall survival and an earlier age at diagnosis with higher rates of adverse cytogenetics. This retrospective analysis of VHA patients compared black and nonblack patients. It found that black patients had worse survival compared to nonblack patients in a single health care delivery system, which limits differences in access to care. Black patients were younger and had shorter periods of observation and were more frequently given first-line fludarabine.

Evaluation of Romyelocel-L Myeloid Progenitor Cells to Decrease Infections in De Novo AML Patients Receiving High-Dose Ara-C-Based Induction Therapy

Induction chemotherapy (7+3) or high-dose ara-C-based (HIDAC) for acute myeloid leukemia (AML) results in prolonged neutropenia with a high risk of serious infection and attendant morbidity, and prolonged hospitalization. Researchers, including former AVAHO president Suman Kambhampati developed a randomized, open-label, controlled Phase 2 trial to study  the effect of romyelocel-L in de novo patients receiving HIDAC or 7+3 induction therapy for reduction of fever and infection. The results from pooled and 7+3 cohorts, were previously presented, showing decrease in infections and days in hospital. The results from cohorts receiving HIDAC chemotherapy are presented here. The incidence of infections was decreased during the day 15-28 period and a decrease of three days in hospital stay was observed in de novo HIDAC AML subjects receiving romyelocel-L. Romyelocel-L may provide a new option to reduce infections in AML patients undergoing HIDAC induction therapy.

Multiple Myeloma

Two studies focused on racial disparities in multiple myeloma (MM), while another reported phase 2 data on a relapsed/refractory option.

With Equal Access and Utilization of Resources, Younger African American Patients Have Superior Survival Compared to Caucasian Patients Diagnosed with Multiple Myeloma at the Veterans Affairs Hospitals

This group of researchers found an absence of disparity in use of novel agents, no racial disparity was observed in overall survival between black and white patients with MM. Among patients aged < 65 years at diagnosis, the researchers observed a significantly lower age-adjusted risk of death for black patients compared with white patients. The difference in the younger population was not explained by access or utilization of resources. This analysis suggests that when healthcare access is neutralized, younger black patients may even have improved overall survival, which may indicate the possibility of genetic differences that may drive the disease biology and therapeutic outcome in AA patients.

Outcomes of Black Patients with Multiple Myeloma in the Veterans Health Administration

The second study found survival of black patients with MM was improved compared to non-blacks in the VHA, a national comprehensive care delivery system. Black patients also received similar therapies compared to non-blacks, while presenting at a younger age with more comorbidities. These results are strengthened after adjusting for treatments and patient characteristics not available in other large data studies. Despite increased incidence of MM in the black population, outcomes are improved, similar to other large studies of patients in the United States.

Immune Profiling of Relapsed or Refractory Multiple Myeloma Patients Treated with Pomalidomide and Low-Dose Dexamethasone in Combination with Daratumumab

Multiple myeloma clinical trial CC-4047-MM-014 (NCT01946477) is a phase 2 study designed to test the safety and efficacy of pomalidomide and low-dose dexamethasone alone (arm A) or in combination with daratumumab, an anti-CD38 antibody, (arm B) subjects with relapsed or refractory MM who have received a first- or second-line treatment of lenalidomide-based therapy. In this trial, researchers (including those from VA facilities, Celgene, and multiple other locations) sought to characterize on-treatment pharmacodynamic changes of immune biomarkers associated with POM + LoDEX + DARA administration (arm B) using multicolor flow cytometry panels designed to characterize T-cell subsets and CD38+ expressing cells. The researchers reported that the triplet regimen POM + LoDEX + DARA has shown notable clinical activity with deep and durable responses in relapsed MM patients progressed and are or refractory to lenalidomide. According to the researchers the results demonstrate that patients treated with the POM + LoDEX + DARA combination do not demonstrate impairment in the innate and adaptive immune compartments and, in contrast, show significant proliferative activity in the subsets of CD4, CD8 and NK cells following treatment.

With hundreds of sessions and thousands of abstracts, it can be difficult to wade through all the new findings to find the most significant and relevant findings. Federal Practitioner consulted with Association of VA Hematology/Oncology members who attended the meeting, VA researchers, and other sources to provide these nuggets you might have missed on lymphomas, white blood cells, leukemias, and multiple myeloma:

Lymphomas

Veterans Treated with R-CHOP for Diffuse Large B Cell Lymphoma Compared to Neighboring Hospital: An Interesting Discovery for Treatment Outcomes

This retrospective analysis of diffuse large B cell lymphoma (DCBL) patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the VA Audie Murphy Hospital in San Antonio, Texas was compared with patients with DLBCL who received R-CHOP in a community setting. According to the researchers, the response to initial treatment was inferior in the veteran population when compared with a patient population with similar demographics and having similar time from diagnosis to treatment. Veteran patients also had worse outcomes when compared with uninsured patients.

Factors Associated with Overall Survival in Follicular Lymphoma Patients Who Are Eligible for Maintenance Therapy

This retrospective analysis study identified 2,290 patients with follicular lymphoma treated in the Veterans Health Administration between 2006–2014 and detailed their staging, demographics, and comorbidities. The researchers found that maintenance therapy with rituximab was associated with an improvement in overall survival.

Treatment Practices and Outcomes in Older Adults with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Treated in the Veterans Health Administration

Another retrospective analysis of DBCL using VHA data examined the effectiveness of second-line chemotherapy and chemoimmunotherapy in patients aged ≥ 65 years. The researchers found 230 patients from 2001 to 2015 that met the inclusion criteria. According to the researchers, the overall survival was < 1 year and about half of the patients "did not receive or were not candidates for regimens typically used with intent for high-dose therapy and autologous transplant."

White Blood Cells

Cost-Effective Use of White Blood Cell Growth Factors in the Veterans Administration

This study analyzed the use of granulocyte colony-stimulating (G-CSF) vs pegfilgrastim in the UD Department of Veterans Affairs (VA) health care system. The researchers looked at the relative frequency of use of filgrastim, Tbo-filgrastim, Filgrastim-sndz and pegfilgrastim at 23 VA sites and found that uptake of biosimilar G-CSF has been extremely rapid. All sites are using biosimilar GCSF for all new patients; 6 of 23 sites were comfortable shifting current patients on branded G-CSF to the biosimilar.However, switching to a Tbo-filgrastim brought a cost savings of 2.2% that was "small compared to other clinical changes."

Elevated White Blood Cell Levels and Thrombotic Events in Patients with Polycythemia Vera: A Real-World Analysis of Veterans Health Administration Data

This analysis described the association between white blood cell (EBC) levels and occurrence of thrombotic events among patients with polycythemia vera (PV) using Veterans Health Administration claims data collected between 2005 and 2012. The researchers found A significant, positive association between increased WBC counts and occurrence of thrombotic events in patients with PV was observed in this study. Patients with WBC counts ≥ 8.5 × 109/L had a significantly increased risk of thrombotic events, and those with counts ≥ 11.0 × 109/L were at greatest risk. Effective control of WBC counts is an important component of disease management and may reduce risk of thrombotic events in patients with PV.

Leukemias

Survival and Treatment of Black Patients with Chronic Lymphocytic Leukemia in the Veterans Health Affairs

Black patients with chronic lymphocytic leukemia tend to have worse overall survival and an earlier age at diagnosis with higher rates of adverse cytogenetics. This retrospective analysis of VHA patients compared black and nonblack patients. It found that black patients had worse survival compared to nonblack patients in a single health care delivery system, which limits differences in access to care. Black patients were younger and had shorter periods of observation and were more frequently given first-line fludarabine.

Evaluation of Romyelocel-L Myeloid Progenitor Cells to Decrease Infections in De Novo AML Patients Receiving High-Dose Ara-C-Based Induction Therapy

Induction chemotherapy (7+3) or high-dose ara-C-based (HIDAC) for acute myeloid leukemia (AML) results in prolonged neutropenia with a high risk of serious infection and attendant morbidity, and prolonged hospitalization. Researchers, including former AVAHO president Suman Kambhampati developed a randomized, open-label, controlled Phase 2 trial to study  the effect of romyelocel-L in de novo patients receiving HIDAC or 7+3 induction therapy for reduction of fever and infection. The results from pooled and 7+3 cohorts, were previously presented, showing decrease in infections and days in hospital. The results from cohorts receiving HIDAC chemotherapy are presented here. The incidence of infections was decreased during the day 15-28 period and a decrease of three days in hospital stay was observed in de novo HIDAC AML subjects receiving romyelocel-L. Romyelocel-L may provide a new option to reduce infections in AML patients undergoing HIDAC induction therapy.

Multiple Myeloma

Two studies focused on racial disparities in multiple myeloma (MM), while another reported phase 2 data on a relapsed/refractory option.

With Equal Access and Utilization of Resources, Younger African American Patients Have Superior Survival Compared to Caucasian Patients Diagnosed with Multiple Myeloma at the Veterans Affairs Hospitals

This group of researchers found an absence of disparity in use of novel agents, no racial disparity was observed in overall survival between black and white patients with MM. Among patients aged < 65 years at diagnosis, the researchers observed a significantly lower age-adjusted risk of death for black patients compared with white patients. The difference in the younger population was not explained by access or utilization of resources. This analysis suggests that when healthcare access is neutralized, younger black patients may even have improved overall survival, which may indicate the possibility of genetic differences that may drive the disease biology and therapeutic outcome in AA patients.

Outcomes of Black Patients with Multiple Myeloma in the Veterans Health Administration

The second study found survival of black patients with MM was improved compared to non-blacks in the VHA, a national comprehensive care delivery system. Black patients also received similar therapies compared to non-blacks, while presenting at a younger age with more comorbidities. These results are strengthened after adjusting for treatments and patient characteristics not available in other large data studies. Despite increased incidence of MM in the black population, outcomes are improved, similar to other large studies of patients in the United States.

Immune Profiling of Relapsed or Refractory Multiple Myeloma Patients Treated with Pomalidomide and Low-Dose Dexamethasone in Combination with Daratumumab

Multiple myeloma clinical trial CC-4047-MM-014 (NCT01946477) is a phase 2 study designed to test the safety and efficacy of pomalidomide and low-dose dexamethasone alone (arm A) or in combination with daratumumab, an anti-CD38 antibody, (arm B) subjects with relapsed or refractory MM who have received a first- or second-line treatment of lenalidomide-based therapy. In this trial, researchers (including those from VA facilities, Celgene, and multiple other locations) sought to characterize on-treatment pharmacodynamic changes of immune biomarkers associated with POM + LoDEX + DARA administration (arm B) using multicolor flow cytometry panels designed to characterize T-cell subsets and CD38+ expressing cells. The researchers reported that the triplet regimen POM + LoDEX + DARA has shown notable clinical activity with deep and durable responses in relapsed MM patients progressed and are or refractory to lenalidomide. According to the researchers the results demonstrate that patients treated with the POM + LoDEX + DARA combination do not demonstrate impairment in the innate and adaptive immune compartments and, in contrast, show significant proliferative activity in the subsets of CD4, CD8 and NK cells following treatment.

With hundreds of sessions and thousands of abstracts, it can be difficult to wade through all the new findings to find the most significant and relevant findings. Federal Practitioner consulted with Association of VA Hematology/Oncology members who attended the meeting, VA researchers, and other sources to provide these nuggets you might have missed on lymphomas, white blood cells, leukemias, and multiple myeloma:

Lymphomas

Veterans Treated with R-CHOP for Diffuse Large B Cell Lymphoma Compared to Neighboring Hospital: An Interesting Discovery for Treatment Outcomes

This retrospective analysis of diffuse large B cell lymphoma (DCBL) patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the VA Audie Murphy Hospital in San Antonio, Texas was compared with patients with DLBCL who received R-CHOP in a community setting. According to the researchers, the response to initial treatment was inferior in the veteran population when compared with a patient population with similar demographics and having similar time from diagnosis to treatment. Veteran patients also had worse outcomes when compared with uninsured patients.

Factors Associated with Overall Survival in Follicular Lymphoma Patients Who Are Eligible for Maintenance Therapy

This retrospective analysis study identified 2,290 patients with follicular lymphoma treated in the Veterans Health Administration between 2006–2014 and detailed their staging, demographics, and comorbidities. The researchers found that maintenance therapy with rituximab was associated with an improvement in overall survival.

Treatment Practices and Outcomes in Older Adults with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Treated in the Veterans Health Administration

Another retrospective analysis of DBCL using VHA data examined the effectiveness of second-line chemotherapy and chemoimmunotherapy in patients aged ≥ 65 years. The researchers found 230 patients from 2001 to 2015 that met the inclusion criteria. According to the researchers, the overall survival was < 1 year and about half of the patients "did not receive or were not candidates for regimens typically used with intent for high-dose therapy and autologous transplant."

White Blood Cells

Cost-Effective Use of White Blood Cell Growth Factors in the Veterans Administration

This study analyzed the use of granulocyte colony-stimulating (G-CSF) vs pegfilgrastim in the UD Department of Veterans Affairs (VA) health care system. The researchers looked at the relative frequency of use of filgrastim, Tbo-filgrastim, Filgrastim-sndz and pegfilgrastim at 23 VA sites and found that uptake of biosimilar G-CSF has been extremely rapid. All sites are using biosimilar GCSF for all new patients; 6 of 23 sites were comfortable shifting current patients on branded G-CSF to the biosimilar.However, switching to a Tbo-filgrastim brought a cost savings of 2.2% that was "small compared to other clinical changes."

Elevated White Blood Cell Levels and Thrombotic Events in Patients with Polycythemia Vera: A Real-World Analysis of Veterans Health Administration Data

This analysis described the association between white blood cell (EBC) levels and occurrence of thrombotic events among patients with polycythemia vera (PV) using Veterans Health Administration claims data collected between 2005 and 2012. The researchers found A significant, positive association between increased WBC counts and occurrence of thrombotic events in patients with PV was observed in this study. Patients with WBC counts ≥ 8.5 × 109/L had a significantly increased risk of thrombotic events, and those with counts ≥ 11.0 × 109/L were at greatest risk. Effective control of WBC counts is an important component of disease management and may reduce risk of thrombotic events in patients with PV.

Leukemias

Survival and Treatment of Black Patients with Chronic Lymphocytic Leukemia in the Veterans Health Affairs

Black patients with chronic lymphocytic leukemia tend to have worse overall survival and an earlier age at diagnosis with higher rates of adverse cytogenetics. This retrospective analysis of VHA patients compared black and nonblack patients. It found that black patients had worse survival compared to nonblack patients in a single health care delivery system, which limits differences in access to care. Black patients were younger and had shorter periods of observation and were more frequently given first-line fludarabine.

Evaluation of Romyelocel-L Myeloid Progenitor Cells to Decrease Infections in De Novo AML Patients Receiving High-Dose Ara-C-Based Induction Therapy

Induction chemotherapy (7+3) or high-dose ara-C-based (HIDAC) for acute myeloid leukemia (AML) results in prolonged neutropenia with a high risk of serious infection and attendant morbidity, and prolonged hospitalization. Researchers, including former AVAHO president Suman Kambhampati developed a randomized, open-label, controlled Phase 2 trial to study  the effect of romyelocel-L in de novo patients receiving HIDAC or 7+3 induction therapy for reduction of fever and infection. The results from pooled and 7+3 cohorts, were previously presented, showing decrease in infections and days in hospital. The results from cohorts receiving HIDAC chemotherapy are presented here. The incidence of infections was decreased during the day 15-28 period and a decrease of three days in hospital stay was observed in de novo HIDAC AML subjects receiving romyelocel-L. Romyelocel-L may provide a new option to reduce infections in AML patients undergoing HIDAC induction therapy.

Multiple Myeloma

Two studies focused on racial disparities in multiple myeloma (MM), while another reported phase 2 data on a relapsed/refractory option.

With Equal Access and Utilization of Resources, Younger African American Patients Have Superior Survival Compared to Caucasian Patients Diagnosed with Multiple Myeloma at the Veterans Affairs Hospitals

This group of researchers found an absence of disparity in use of novel agents, no racial disparity was observed in overall survival between black and white patients with MM. Among patients aged < 65 years at diagnosis, the researchers observed a significantly lower age-adjusted risk of death for black patients compared with white patients. The difference in the younger population was not explained by access or utilization of resources. This analysis suggests that when healthcare access is neutralized, younger black patients may even have improved overall survival, which may indicate the possibility of genetic differences that may drive the disease biology and therapeutic outcome in AA patients.

Outcomes of Black Patients with Multiple Myeloma in the Veterans Health Administration

The second study found survival of black patients with MM was improved compared to non-blacks in the VHA, a national comprehensive care delivery system. Black patients also received similar therapies compared to non-blacks, while presenting at a younger age with more comorbidities. These results are strengthened after adjusting for treatments and patient characteristics not available in other large data studies. Despite increased incidence of MM in the black population, outcomes are improved, similar to other large studies of patients in the United States.

Immune Profiling of Relapsed or Refractory Multiple Myeloma Patients Treated with Pomalidomide and Low-Dose Dexamethasone in Combination with Daratumumab

Multiple myeloma clinical trial CC-4047-MM-014 (NCT01946477) is a phase 2 study designed to test the safety and efficacy of pomalidomide and low-dose dexamethasone alone (arm A) or in combination with daratumumab, an anti-CD38 antibody, (arm B) subjects with relapsed or refractory MM who have received a first- or second-line treatment of lenalidomide-based therapy. In this trial, researchers (including those from VA facilities, Celgene, and multiple other locations) sought to characterize on-treatment pharmacodynamic changes of immune biomarkers associated with POM + LoDEX + DARA administration (arm B) using multicolor flow cytometry panels designed to characterize T-cell subsets and CD38+ expressing cells. The researchers reported that the triplet regimen POM + LoDEX + DARA has shown notable clinical activity with deep and durable responses in relapsed MM patients progressed and are or refractory to lenalidomide. According to the researchers the results demonstrate that patients treated with the POM + LoDEX + DARA combination do not demonstrate impairment in the innate and adaptive immune compartments and, in contrast, show significant proliferative activity in the subsets of CD4, CD8 and NK cells following treatment.

SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.

The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.

The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.

However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.

In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.

The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.

Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.

Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.

The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.

Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”

In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.

Dr. Gray reported having no disclosures.

SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.

SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.

The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.

The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.

However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.

In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.

The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.

Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.

Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.

The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.

Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”

In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.

Dr. Gray reported having no disclosures.

SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.

SAN ANTONIO – Extending aromatase inhibitor (AI) therapy an additional 5 years reduces breast cancer recurrence risk, particularly in patients with node involvement, but the benefits vary based on prior treatment and must be weighed against the risk of bone fracture, according to findings from a meta-analysis involving more than 22,000 women.

The rate of any recurrence after 10 years in almost 7,500 women treated with 5 years of tamoxifen and then randomized to 5 additional years of AI treatment was reduced by 35%, compared with the rate in those who did not receive 5 additional years of AI therapy (recurrence rate, 10.7% vs. 7.1%, respectively; relative risk, 0.67), and the difference was “very highly significant,” Richard Gray, MD, reported at the San Antonio Breast Cancer Symposium.

The distant recurrence rate and mortality rate were also significantly improved in those who received 5 years of AI therapy (rr, 0.77 for each), but the difference in mortality was of borderline significance, Dr. Gray, professor of medical statistics at the University of Oxford, London, reported on behalf of the Early Breast Cancer Trialists’ Collaborative Group.

However, in many of the trials included in the analysis, control group patients crossed over to the treatment group, which likely reduced the effect, he noted.

In about 12,000 women who were treated with 2-3 years of tamoxifen followed by 2-3 years of an AI and who were then randomized to an additional 3-5 years of AI therapy, the effects were less pronounced, with about a 20% reduced risk of any recurrence after 10 years vs. the rate in those without extended therapy (recurrence rate, 9.2% vs. 7.1%), he said.

The differences in the rates of distant recurrence and breast cancer mortality were not statistically significant in this group, but again, follow-up was short, he said.

Similarly, in about 3,300 women treated with an AI followed by an additional 5 years of AI therapy, recurrence risk was reduced by about 25% vs. the rate in those who did not receive extended therapy, and no difference was seen in the rates of distant recurrence or breast cancer mortality.

Of note, the benefits in those who received tamoxifen were seen immediately, whereas the benefits in those receiving AIs in the first 5 years emerged after about 2 years of extended therapy, Dr. Gray said, explaining that this was likely due to “carry-over benefits” of the earlier AI therapy.

The downside with extended AI therapy was a 25% increase in fracture risk, as well as bone pain, which can reduce quality of life.

Therefore, decisions about extended therapy should involve careful risk-benefit analyses, he said, adding that the findings of this meta-analysis of 12 trials, which included postmenopausal women – 99% of whom had estrogen receptor–positive disease – provide “the most reliable assessment of the available evidence ... [for] guiding decisions about endocrine therapy.”

In this video interview, he further discussed the details and limitations of the study, the effects of nodal status on outcomes, implications of the findings for clinical practice, the need for further follow-up on all of the studies included in the analysis, and plans for incorporating new data from the AERAS trial, which were also presented at the symposium and which complement and reinforce the current findings.

Dr. Gray reported having no disclosures.

SOURCE: Gray R et al., SABCS 2018: Abstract GS3-03.

A significant number of patients who receive only a placebo in a clinical trial of cancer immunotherapy still experience grade three or grade four adverse events, research suggests.

Writing in JAMA Network Open, researchers reported the outcomes of a systematic review and meta-analysis of 10 randomized, double-blind, placebo-controlled, phase 3 trials of targeted therapy or immunotherapy drugs for cancer, in which patients in the placebo group were treated only with placebo and no other anticancer drugs.

Among the 4,873 patients who were randomized to placebo, a mean of 85.1% experienced some sort of placebo adverse event. The overall incidence of grade 3-4 placebo adverse events was 18% but was as high as 25% in two trials – one in renal cell carcinoma and one in melanoma – and as low as 11% in one trial.

Hypertension was the most frequent grade 3-4 adverse event among patients on placebo, experienced by a mean of 2.8% of patients, followed by fatigue (1%) and diarrhea (0.8%).

Neither route of administration nor cancer type made a significant difference in terms of the rate of placebo adverse events. No deaths attributed to the placebo were reported, but the mean rate of discontinuation due to placebo adverse events was 3.9%, and was higher than 5% for four trials.

The median duration of placebo administration ranged from 10 to 15 months for all but one study, and the authors noted that the longer the placebo exposure, the higher the proportion of grade 3-4 adverse events.

The investigators – Matías Rodrigo Chacón, MD, and his colleagues in the research department at the Argentine Association of Clinical Oncology – said that studies with a lower incidence of grade 3-4 adverse events in the treatment arm also had a lower incidence of grade 3-4 placebo adverse events, while the higher incidences of placebo adverse events were seen in studies that also had a higher incidence of treatment-related adverse events.

They suggested that “contextual factors,” such as the information given during the informed consent process, could contribute to negative expectations of adverse events.

“To illustrate this point, in an RCT [randomized controlled trial] of aspirin as a treatment for unstable angina, a higher incidence of gastrointestinal irritation was reported in centers that specified its potential occurrence in the informed consent compared with research units that did not include that risk,” they wrote.

They also suggested that patients may experience anxiety associated with the uncertainty about whether they had received active treatment or placebo, and this could also affect their distress levels.

No conflicts of interest were declared.

SOURCE: Chacón M et al. JAMA Network Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5617.

A significant number of patients who receive only a placebo in a clinical trial of cancer immunotherapy still experience grade three or grade four adverse events, research suggests.

Writing in JAMA Network Open, researchers reported the outcomes of a systematic review and meta-analysis of 10 randomized, double-blind, placebo-controlled, phase 3 trials of targeted therapy or immunotherapy drugs for cancer, in which patients in the placebo group were treated only with placebo and no other anticancer drugs.

Among the 4,873 patients who were randomized to placebo, a mean of 85.1% experienced some sort of placebo adverse event. The overall incidence of grade 3-4 placebo adverse events was 18% but was as high as 25% in two trials – one in renal cell carcinoma and one in melanoma – and as low as 11% in one trial.

Hypertension was the most frequent grade 3-4 adverse event among patients on placebo, experienced by a mean of 2.8% of patients, followed by fatigue (1%) and diarrhea (0.8%).

Neither route of administration nor cancer type made a significant difference in terms of the rate of placebo adverse events. No deaths attributed to the placebo were reported, but the mean rate of discontinuation due to placebo adverse events was 3.9%, and was higher than 5% for four trials.

The median duration of placebo administration ranged from 10 to 15 months for all but one study, and the authors noted that the longer the placebo exposure, the higher the proportion of grade 3-4 adverse events.

The investigators – Matías Rodrigo Chacón, MD, and his colleagues in the research department at the Argentine Association of Clinical Oncology – said that studies with a lower incidence of grade 3-4 adverse events in the treatment arm also had a lower incidence of grade 3-4 placebo adverse events, while the higher incidences of placebo adverse events were seen in studies that also had a higher incidence of treatment-related adverse events.

They suggested that “contextual factors,” such as the information given during the informed consent process, could contribute to negative expectations of adverse events.

“To illustrate this point, in an RCT [randomized controlled trial] of aspirin as a treatment for unstable angina, a higher incidence of gastrointestinal irritation was reported in centers that specified its potential occurrence in the informed consent compared with research units that did not include that risk,” they wrote.

They also suggested that patients may experience anxiety associated with the uncertainty about whether they had received active treatment or placebo, and this could also affect their distress levels.

No conflicts of interest were declared.

SOURCE: Chacón M et al. JAMA Network Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5617.

A significant number of patients who receive only a placebo in a clinical trial of cancer immunotherapy still experience grade three or grade four adverse events, research suggests.

Writing in JAMA Network Open, researchers reported the outcomes of a systematic review and meta-analysis of 10 randomized, double-blind, placebo-controlled, phase 3 trials of targeted therapy or immunotherapy drugs for cancer, in which patients in the placebo group were treated only with placebo and no other anticancer drugs.

Among the 4,873 patients who were randomized to placebo, a mean of 85.1% experienced some sort of placebo adverse event. The overall incidence of grade 3-4 placebo adverse events was 18% but was as high as 25% in two trials – one in renal cell carcinoma and one in melanoma – and as low as 11% in one trial.

Hypertension was the most frequent grade 3-4 adverse event among patients on placebo, experienced by a mean of 2.8% of patients, followed by fatigue (1%) and diarrhea (0.8%).

Neither route of administration nor cancer type made a significant difference in terms of the rate of placebo adverse events. No deaths attributed to the placebo were reported, but the mean rate of discontinuation due to placebo adverse events was 3.9%, and was higher than 5% for four trials.

The median duration of placebo administration ranged from 10 to 15 months for all but one study, and the authors noted that the longer the placebo exposure, the higher the proportion of grade 3-4 adverse events.

The investigators – Matías Rodrigo Chacón, MD, and his colleagues in the research department at the Argentine Association of Clinical Oncology – said that studies with a lower incidence of grade 3-4 adverse events in the treatment arm also had a lower incidence of grade 3-4 placebo adverse events, while the higher incidences of placebo adverse events were seen in studies that also had a higher incidence of treatment-related adverse events.

They suggested that “contextual factors,” such as the information given during the informed consent process, could contribute to negative expectations of adverse events.

“To illustrate this point, in an RCT [randomized controlled trial] of aspirin as a treatment for unstable angina, a higher incidence of gastrointestinal irritation was reported in centers that specified its potential occurrence in the informed consent compared with research units that did not include that risk,” they wrote.

They also suggested that patients may experience anxiety associated with the uncertainty about whether they had received active treatment or placebo, and this could also affect their distress levels.

No conflicts of interest were declared.

SOURCE: Chacón M et al. JAMA Network Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5617.

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.

Susan London/MDedge News

“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”

The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.

“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”

“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”

 

 

Study details

For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.

Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.

Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.

Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.

The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.

Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).

Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.

“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.

SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.

Susan London/MDedge News

“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”

The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.

“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”

“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”

 

 

Study details

For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.

Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.

Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.

Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.

The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.

Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).

Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.

“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.

SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.

Susan London/MDedge News

“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”

The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.

“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”

“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”

 

 

Study details

For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.

Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.

Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.

Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.

The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.

Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).

Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.

“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.

SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.

Although patients with multiple myeloma (MM) have an increased risk of developing venous thromboembolism (VTE), no validated model exists that predicts VTE in MM. To help health care providers better assess the risks and the appropriateness of thromboprophylaxis, a team of researchers have developed the IMPEDE VTE risk assessment tool.

According to Kristen M. Sanfilippo, MD, of Washington University School of Medicine and the St. Louis Veterans Affairs Medical Center in Missouri, who presented the paper at the American Society of Hematology meeting last week in San Diego, this is the first effort to build a tool that is both internally and externally validated. The goal was to develop a model that outperformed current National Comprehensive Cancer Network (NCCN) guidelines for VTE that are based on expert opinion and were not specific to patients with multiple myeloma.

“We evaluated the performance of the current NCCN and International Myeloma Working Group guidelines with the VA data and our model outperformed these guidelines. Our recommendations is that our IMPEDE VTE should be considered to replace them,” said Sanfilippo. "I think we can improve our predictability of thrombosis in myeloma by adding novel predictors to the model, but that would have to be assessed in a prospective manner.”

Using the VA Central Cancer Registry, the researchers identified 4,448 patients diagnosed with MM between 1999 and 2014 and retrospectively followed the patients for 180 days after start of MM chemotherapy. Using beta coefficients, the researchers developed a risk score by dividing by a common divisor and rounding to the nearest integer. The risk score for each patient was the sum of all scores for each predictor variable.

The factors associated with VTE were combined to develop the IMPEDE VTE score. The factors were: Immunomodulatory drugs, 3 points; BMI > 25,  1 point; Pathologic fracture pelvis/femur 2 points; Erythropoiesis-stimulating agents, 1 point, Dexamethasone (High-dose 4 points; low-dose 2 points)/Doxorubicin 2 points; Asian Ethnicity, -3 points; history of VTE, 3 points; Tunneled line/ central venous catheter, 2 points). In addition, use of therapeutic anticoagulation (-5 points) with warfarin or low molecular weight heparin (LWMH) and use of prophylactic LMWH or aspirin (-2 points) were associated with a decreased risk of VTE. The risk score then identifies patients’ VTE risk as low (≤ 3), intermediate (4-6), or high (≥ 7).

According to Sanfilippo, the model showed satisfactory discrimination in both the derivation cohort (Harrell’s c-statistic = 0.66) and in the bootstrap validation, c-statistic = 0.66 (95% CI: 0.63 – 0.70). Within the first 6-months of starting chemotherapy, the rate of VTE was 3.5% compared to > 10% for high-risk patients.

The researchers hoped that the risk prediction model for VTE in MM would allow for use of thromboprophylaxis in MM patients at high-risk of VTE while sparing those at low risk. 

Although patients with multiple myeloma (MM) have an increased risk of developing venous thromboembolism (VTE), no validated model exists that predicts VTE in MM. To help health care providers better assess the risks and the appropriateness of thromboprophylaxis, a team of researchers have developed the IMPEDE VTE risk assessment tool.

According to Kristen M. Sanfilippo, MD, of Washington University School of Medicine and the St. Louis Veterans Affairs Medical Center in Missouri, who presented the paper at the American Society of Hematology meeting last week in San Diego, this is the first effort to build a tool that is both internally and externally validated. The goal was to develop a model that outperformed current National Comprehensive Cancer Network (NCCN) guidelines for VTE that are based on expert opinion and were not specific to patients with multiple myeloma.

“We evaluated the performance of the current NCCN and International Myeloma Working Group guidelines with the VA data and our model outperformed these guidelines. Our recommendations is that our IMPEDE VTE should be considered to replace them,” said Sanfilippo. "I think we can improve our predictability of thrombosis in myeloma by adding novel predictors to the model, but that would have to be assessed in a prospective manner.”

Using the VA Central Cancer Registry, the researchers identified 4,448 patients diagnosed with MM between 1999 and 2014 and retrospectively followed the patients for 180 days after start of MM chemotherapy. Using beta coefficients, the researchers developed a risk score by dividing by a common divisor and rounding to the nearest integer. The risk score for each patient was the sum of all scores for each predictor variable.

The factors associated with VTE were combined to develop the IMPEDE VTE score. The factors were: Immunomodulatory drugs, 3 points; BMI > 25,  1 point; Pathologic fracture pelvis/femur 2 points; Erythropoiesis-stimulating agents, 1 point, Dexamethasone (High-dose 4 points; low-dose 2 points)/Doxorubicin 2 points; Asian Ethnicity, -3 points; history of VTE, 3 points; Tunneled line/ central venous catheter, 2 points). In addition, use of therapeutic anticoagulation (-5 points) with warfarin or low molecular weight heparin (LWMH) and use of prophylactic LMWH or aspirin (-2 points) were associated with a decreased risk of VTE. The risk score then identifies patients’ VTE risk as low (≤ 3), intermediate (4-6), or high (≥ 7).

According to Sanfilippo, the model showed satisfactory discrimination in both the derivation cohort (Harrell’s c-statistic = 0.66) and in the bootstrap validation, c-statistic = 0.66 (95% CI: 0.63 – 0.70). Within the first 6-months of starting chemotherapy, the rate of VTE was 3.5% compared to > 10% for high-risk patients.

The researchers hoped that the risk prediction model for VTE in MM would allow for use of thromboprophylaxis in MM patients at high-risk of VTE while sparing those at low risk. 

Although patients with multiple myeloma (MM) have an increased risk of developing venous thromboembolism (VTE), no validated model exists that predicts VTE in MM. To help health care providers better assess the risks and the appropriateness of thromboprophylaxis, a team of researchers have developed the IMPEDE VTE risk assessment tool.

According to Kristen M. Sanfilippo, MD, of Washington University School of Medicine and the St. Louis Veterans Affairs Medical Center in Missouri, who presented the paper at the American Society of Hematology meeting last week in San Diego, this is the first effort to build a tool that is both internally and externally validated. The goal was to develop a model that outperformed current National Comprehensive Cancer Network (NCCN) guidelines for VTE that are based on expert opinion and were not specific to patients with multiple myeloma.

“We evaluated the performance of the current NCCN and International Myeloma Working Group guidelines with the VA data and our model outperformed these guidelines. Our recommendations is that our IMPEDE VTE should be considered to replace them,” said Sanfilippo. "I think we can improve our predictability of thrombosis in myeloma by adding novel predictors to the model, but that would have to be assessed in a prospective manner.”

Using the VA Central Cancer Registry, the researchers identified 4,448 patients diagnosed with MM between 1999 and 2014 and retrospectively followed the patients for 180 days after start of MM chemotherapy. Using beta coefficients, the researchers developed a risk score by dividing by a common divisor and rounding to the nearest integer. The risk score for each patient was the sum of all scores for each predictor variable.

The factors associated with VTE were combined to develop the IMPEDE VTE score. The factors were: Immunomodulatory drugs, 3 points; BMI > 25,  1 point; Pathologic fracture pelvis/femur 2 points; Erythropoiesis-stimulating agents, 1 point, Dexamethasone (High-dose 4 points; low-dose 2 points)/Doxorubicin 2 points; Asian Ethnicity, -3 points; history of VTE, 3 points; Tunneled line/ central venous catheter, 2 points). In addition, use of therapeutic anticoagulation (-5 points) with warfarin or low molecular weight heparin (LWMH) and use of prophylactic LMWH or aspirin (-2 points) were associated with a decreased risk of VTE. The risk score then identifies patients’ VTE risk as low (≤ 3), intermediate (4-6), or high (≥ 7).

According to Sanfilippo, the model showed satisfactory discrimination in both the derivation cohort (Harrell’s c-statistic = 0.66) and in the bootstrap validation, c-statistic = 0.66 (95% CI: 0.63 – 0.70). Within the first 6-months of starting chemotherapy, the rate of VTE was 3.5% compared to > 10% for high-risk patients.

The researchers hoped that the risk prediction model for VTE in MM would allow for use of thromboprophylaxis in MM patients at high-risk of VTE while sparing those at low risk.